研究・研究者
研究会・セミナー
| 演 題 | 「Transient biomolecule complexes at atomic resolution by solution NMR spectroscopy」 |
|---|---|
| 日 時 | 2012年11月13日(火) 14:00 より 15:00 まで |
| 講演者 | Dr. Nicolas L. Fawzi (National Institutes of Health, USA) |
| 場 所 | 山手3号館2階共通セミナー室 |
| 概 要 | Complex networks of biomolecular interactions are precisely tuned for normal biological processes and disease can result when regulation mechanisms fail. Among techniques for the observation of these functional biological interactions at atomic resolution, nuclear magnetic resonance (NMR) spectroscopy is particularly well suited to the study of motions and binding pathways in a native solution environment, revealing mechanistic details not evident in single, static pictures. To begin, I will describe a method to distinguish different classes of transient protein-protein encounter complexes formed during the search for the active complex. Sensitive to these sparsely populated states, paramagnetic relaxation enhancement techniques combined with titration revealed structurally distinct encounter complex populations, each with a different potential function. Second, I will describe work using a new solution NMR technique to investigate the formation of aggregates of the amyloid b (Aβ) peptide, linked to neurotoxicity in Alzheimer’s Disease. Dark-state Exchange Saturation Transfer (DEST) exploits the exchange between monomers free in solution and bound to large, protofibril aggregates to imprint the dynamics of the protofibril-bound species onto the easily observed NMR spectrum of the monomer. Slower bound-state dynamics observed for the C-terminal residues of Aβ42 relative to Aβ40 may explain the former’s higher propensity for rapid aggregation and high correlation with disease severity. The DEST technique for determining the dynamics at single residue resolution of otherwise invisible 'dark' states will be applicable to areas of current interest including the interaction of unfolded proteins with the proteasome and very large chaperones, the binding of soluble proteins to membrane-bound receptors, and the folding-upon-binding of intrinsically disordered proteins. |
| その他 | 主催 分子科学研究所 分子スケールナノサイエンスセンター |
| お問合せ先 | 加藤晃一 |
